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Glucotrol®; Glucotrol® XL
Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Crosses the placenta. Abnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy. If glipizide is used during pregnancy, discontinue and change to insulin at least 1 month prior to delivery to decrease prolonged hypoglycemia in the neonate.
Excretion in breast milk unknown/not recommended
Hypersensitivity to glipizide or any component of the formulation, other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM)
Use with caution in patients with severe hepatic disease.
Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
The extended release formulation consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction. Avoid use of extended release tablets (Glucotrol® XL) in patients with severe gastrointestinal narrowing or esophageal dysmotility.
Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
Frequency not defined.
Cardiovascular: Edema, syncope
Central nervous system: Anxiety, depression, dizziness, headache, insomnia, nervousness
Dermatologic: Rash, urticaria, photosensitivity, pruritus
Endocrine & metabolic: Hypoglycemia, hyponatremia, SIADH (rare)
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, epigastric fullness, constipation, heartburn, flatulence
Hematologic: Blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis
Hepatic: Cholestatic jaundice, hepatic porphyria
Neuromuscular & skeletal: Arthralgia, leg cramps, myalgia, tremor
Ocular: Blurred vision
Renal: Diuretic effect (minor)
Miscellaneous: Diaphoresis, disulfiram-like reaction
Postmarketing and/or case reports: Abdominal pain
Symptoms of overdose include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Intoxication with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms).
of 2C8/9 (major)Substrate
Anabolic steroids may increase hypoglycemic effect; monitor blood glucose.
ACE inhibitors may increase hypoglycemic effect; monitor blood glucose.
Beta-blockers decrease hypoglycemic effect, mask most hypoglycemic symptoms, decrease glycogenolysis; avoid use in diabetics with frequent hypoglycemic episodes.
Cholestyramine decreases glipizide's absorption; separate administration times.
Corticosteroids cause hyperglycemia; adjustment of hypoglycemic agent may be necessary.
Cyclosporine serum concentration is increased; monitor cyclosporine levels and renal function.
CYP2C8/9 inducers: May decrease the levels/effects of glipizide. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C8/9 inhibitors: May increase the levels/effects of glipizide. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Ethanol (large amounts) decreases hypoglycemic effect; avoid concurrent use; rare disulfiram reaction.
H2 antagonists, antacids, oral sodium bicarbonate may increase the hypoglycemic effect; monitor glucose response.
Rifampin may decrease hypoglycemic effects of glipizide; monitor blood glucose.
Tacrolimus serum concentrations may be increased; monitor tacrolimus serum concentrations and renal function.
Ethanol: Caution with ethanol (may cause hypoglycemia or rare disulfiram reaction).
Food: A delayed release of insulin may occur if glipizide is taken with food. Immediate release tablets should be administered 30 minutes before meals to avoid erratic absorption.
Herb/Nutraceutical: Caution with chromium, garlic, gymnema (may cause hypoglycemia).
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Onset of action: Peak effect: Blood glucose reductions: 1.5-2 hours
Duration: 12-24 hours
Absorption: Delayed with food
Protein binding: 92% to 99%
Metabolism: Hepatic with metabolites
Half-life elimination: 2-4 hours
Excretion: Urine (60% to 80%, 91% to 97% as metabolites); feces (11%)
Oral (allow several days between dose titrations): Adults: Initial: 5 mg/day; adjust dosage at 2.5-5 mg daily increments as determined by blood glucose response at intervals of several days.
Immediate release tablet: Maximum recommended once-daily dose: 15 mg; maximum recommended total daily dose: 40 mg
Extended release tablet (Glucotrol® XL): Maximum recommended dose: 20 mg
When transferring from insulin to glipizide:
Current insulin requirement
Current insulin requirement >20 units: Decrease insulin by 50% and initiate glipizide at usual dose; gradually decrease insulin dose based on patient response. Several days should elapse between dosage changes.
Elderly: Initial: 2.5 mg/day; increase by 2.5-5 mg/day at 1- to 2-week intervals
Dosing adjustment/comments in renal impairment: Clcr<10 mL/minute: Some investigators recommend not using
Dosing adjustment in hepatic impairment: Initial dosage should be 2.5 mg/day
Administer immediate release tablets 30 minutes before a meal to achieve greatest reduction in postprandial hyperglycemia. Extended release tablets should be given with breakfast. Patients who are NPO may need to have their dose held to avoid hypoglycemia.
Urine for glucose and ketones; monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), fasting blood glucose, hemoglobin A1c, fructosamine
Target range: Adults:
Fasting blood glucose: <120 mg/dL
Glycosylated hemoglobin: <7%
Take immediate release tablets 30 minutes before meals; extended release tablets should be taken with breakfast. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). Always carry quick source of sugar with you. Take exactly as directed. Immediate release tablets should be taken 30 minutes before meals, at the same time each day. Extended release tablets should be taken with breakfast. Do not chew or crush extended release tablets. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); or headache or nausea (consult prescriber if these persist). Report severe or persistent side effects (eg, hypoglycemia: palpitations, sweaty palms, lightheadedness; extended vomiting; diarrhea or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool). Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.Pregnancy/breast-feeding precautions:
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in diabetic patients treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in diabetic patients receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Glipizide-dependent diabetics (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.
No information available to require special precautions
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glipizide hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects
Tablet (Glucotrol®): 5 mg, 10 mg
Tablet, extended release: 5 mg, 10 mg
(Glucotrol® XL): 2.5 mg, 5 mg, 10 mg
Alexander RW, "Prolonged Hypoglycemia Following Acetohexamide Administration,"Diabetes, 1966, 15(5):362-4.
"A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,"Diabetes, 1976, 25(12):1129-53.
Berelowitz M, Fischette C, Cefalu W, et al, "Comparative Efficacy of a Once-Daily Controlled-Release Formulation of Glipizide and Immediate-Release Glipizide in Patients With NIDDM,"Diabetes Care, 1994, 17(12):1460-4.
Brodows RG, "Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,"Diabetes Care, 1992, 15(1):75-80.
Cowen DL, Burtis B, and Youmans J, "Prolonged Coma After Acetohexamide Ingestion,"JAMA, 1967, 201(2):141-2.
"Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):854-65.
Frederick KA and Wang RY, "Delayed Hypoglycemia in a Child After Ingestion of a Single Glipizide Tablet,"Vet Hum Toxicol, 1994, 35:365.
Garratt KN, Brady PA, Hassinger NL, et al, "Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,"J Am Coll Cardiol, 1999, 33(1):119-24.
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"Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):837-53.
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Aldiab® (ID); Antidiab® (CZ, PL, RU, SI); Apamid® (NO, TH); Beapizide® (SG); Depizide® (TH); Diasef® (SG, TH); Dipazide® (TH); Gipzide® (TH); Glibenese® (AT, BE, CH, DK, ES, FI); Glibénèse® (FR); Glibenese® (GB, IE, LU, NL, PL, RU, YU); Glipazid® (BR); Glipicontin® (IN); Glipid® (NZ); Glipizide DHA® (SG); Glipizide® (GB, PL); Glipizide Shin Poong® (SG); Glipizid Meda® (SE); Glipizid® (NO, RO); Glizide® (TH); Glucodiab® (TH); Gluco-Rite® (IL); Glucotrol® (ID, RO, SI, TR, YU); Glupitel® (MX); Glygen® (TH); Glynase® (IN); Glyzid® (ID); Glyzip® (IN); Linodiab® (ID); Melizide® (AU, TH); Melizid® (FI); Mindiab® (BR, DK, FI, NO, SE); Minidiab® (AT, AU, BE, BG, BR, CL, CZ, FR, HU, ID, IT, LU, NO, NZ, PL, PT, RO, RU, SG, TH, TR); Minodiab® (AR, ES, GB, MX); Ozidia® (FR); Pezide® (TH); Sucrazide® (HK, JO, KW, LB, MT, MY, RO); Xiprine® (CL)